We have recently shown that hepatitis B virus (HBV) core antigen (HBcAg) is the major viral factor for HBV clearance using a hydrodynamics-based mouse model. Knockout of HBcAg hampers the development of antiviral immune responses and thus promotes HBV persistence. Here, we further demonstrated that only in the capsid form, but not the free or dimer form, can HBcAg exert its contributory role in HBV clearance. HBcAg is the main structural protein of HBV icosahedral nucleocapsid. A mutant HBV DNA which expresses an assembly-defective HBcAg, HBcAgY132A, surprisingly prolonged HBV surface antigenemia in both C57BL/6 and BALB/c mice without affecting viral transcription and translation. This result was not due to a loss of the possible immune epitope caused by the single-amino-acid substitution of HBcAg. Moreover, the particular HBV mutant failed to induce robust humoral and cellular immunity against HBV. These data revealed the requirement of capsid structure for inducing adequate immunity that leads to HBV clearance in mice.

The Ca2+/calmodulin (CaM) signaling pathway mediates the heat stress (HS) response and acquisition of thermotolerance in plants. We showed that the rice CaM1-1 isoform can interpret a Ca2+ signature difference in amplitude, frequency, and temporal–spatial properties in regulating transcription of nucleoplasmic small heat-shock protein gene (sHSPC/N) during HS. Ca2+ and A23187 treatments under HS generated an intense and sustained increase in [Ca2+]cyt and accelerated the expression of CaM1-1 and sHSPC/N genes, which suggests that HS-induced apoplastic Ca2+ influx was responsible for the [Ca2+]cyt transient and downstream HS signaling. Here, we discuss an emerging paradigm in the oscillation regulation of CaM1-1 expression during HS and highlight the areas that need further investigation.

γ-H2AX (activated histone 2AX) and pChk2 (activated checkpoint kinase 2), which are DNA damage response molecules, are produced in irradiated cells and may be signature molecules of radiation exposure. We investigated their use as potential biomarkers to identify individuals exposed to ionizing radiation. We collected exfoliated oral epithelial cell samples from 100 healthy individuals undergoing routine dental radiographic examination (2.34 cGy) both before and after the radiograph using a non-invasive technique. The expression levels of pChk2 and γ-H2AX in oral cells were assessed by immunohistochemical assay. Both biomarkers showed statistically significant increases in levels of expression after the radiation exposure (P < 0.001). This suggests that pChk2 and γ-H2AX may serve as sensitive indicators of low-dose radiation exposure.

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.

We describe here a GC/MS/MS method for the sensitive and concurrent determination of extracellular tryptophan and the kynurenine pathway metabolites kynurenine, 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) in rat brain. This metabolic cascade is increasingly linked to the pathophysiology of several neurological and psychiatric diseases. Methodological refinements, including optimization of MS conditions and addition of deuterated standards, resulted in assay linearity to the low nanomolar range. Measured in samples obtained by striatal microdialysis in vivo, basal levels of tryptophan, kynurenine and QUIN were 415, 89 and 8 nM, respectively, but 3-HK levels were below the limit of detection (<2 nM). Systemic injection of kynurenine (100 mg/kg, i.p.) did not affect extracellular tryptophan but produced detectable levels of extracellular 3-HK (peak after 2-3 h: ~50 nM) and raised extracellular QUIN levels (peak after 2 h: ~105 nM). The effect of this treatment on QUIN, but not on 3-HK, was potentiated in the NMDA-lesioned striatum. Our results indicate that the novel methodology, which allowed the measurement of extracellular kynurenine and 3-HK in the brain in vivo, will facilitate studies of brain kynurenines and of the interplay between peripheral and central kynurenine pathway function under physiological and pathological conditions.

For the first time, we have investigated the bacterial toxicity or compatibility properties of Pt nanoparticles (NPs) with different sizes (P1, P2, P3, P4 and P5). The bacterio-toxic or compatible properties of these five different sized Pt NPs with the clinical pathogen, Pseudomonas aeruginosa were explored by many analytical methods such as the conventional plate count method, matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS), fluorescence microscopy and fluorescence sensoring techniques. The results revealed that the 1–3 nm sized (P1 and P2) Pt NPs showed bacterio-toxic properties while the 4–21 nm (P3, P4 and P5) Pt NPs exhibited bacterio-compatible properties. This is the first study which reports the bacterial toxicity of Pt NPs. The information released from this study is significantly important to future clinical, medical, biological and biomedical applications of Pt NPs.

Intrinsic polarization of ferroelectrics (FE) helps separate photon-generated charge carriers thus enhances photovoltaic effects. However, traditional FE with transition-metal cations (M) of d0 electron in MO6 network typically has a band gap (Eg) exceeding 3.0 eV. Although a smaller Eg (2.6 eV) can be obtained in multiferroic BiFeO3, the value is still too high for optimal solar energy applications. Computational “materials genome” searches have predicted several exotic MO6 FE with Eg < 2.0 eV, all thus far unconfirmed because of synthesis difficulties. Here we report a new FE compound with MO4 tetrahedral network, KBiFe2O5, which features narrow Eg (1.6 eV), high Curie temperature (Tc ~ 780 K) and robust magnetic and photoelectric activities. The high photovoltage (8.8 V) and photocurrent density (15 μA/cm2) were obtained, which is comparable to the reported BiFeO3. This finding may open a new avenue to discovering and designing optimal FE compounds for solar energy applications.

Background

Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. Detection of aberrant methylation in white blood cells (WBC) has been suggested as a marker for cancer development, but has not been extensively investigated. This study was carried out to determine whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for breast cancer risk.

Patients and Methods

Promoter hypermethylation of 8 tumor suppressor genes (RASSF1A, APC, HIN1, BRCA1, cyclinD1, RARβ, CDH1 and TWIST1) and DNA methylation for three repetitive elements (LINE1, Sat2M1 and AluM2) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients by the MethyLight assay. Methylation in WBC from 40 controls was also analyzed.

Results

Tumor and adjacent tissues showed frequent hypermethylation for all genes tested, while WBC DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1 there was agreement between hypermethylation in tumor and adjacent tissues (P=0.04, P=0.02, P=0.005 and P<0.0001, respectively). DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant correlations in the methylation of Sat2M1 between tumor and adjacent tissues and WBC DNA were found (P<0.0001 and P=0.046, respectively). There was also a significant difference in methylation of Sat2M1 between cases and controls (P=0.01).

Conclusion

These results suggest that further studies of WBC methylation, including prospective studies, may provide biomarkers of breast cancer risk.

Summary

Serine-rich repeat glycoproteins (SRRPs) are important bacterial adhesins that are conserved in streptococci and staphylococci. Fimbriae-associated protein (Fap1) from Streptococcus parasanguinis, was the first SRRP identified; it plays an important role in bacterial biofilm formation. A gene cluster encoding glycosyltransferases and accessory secretion components is required for Fap1 biogenesis. Two glycosylation-associated proteins, Gap1 and Gap3 within the cluster, interact with each other and function in concert in Fap1 biogenesis. Here we report the new molecular events underlying contribution of the interaction to Fap1 biogenesis. The Gap1 deficient mutant rendered Gap3 unstable and degraded in vitro and in vivo. Inactivation of a gene encoding protease ClpP reversed the phenotype of the gap1 mutant, suggesting that ClpP is responsible for degradation of Gap3. Molecular chaperone GroEL was co-purified with Gap3 only when Gap1 was absent and also reacted with Gap1 monoclonal antibody, suggesting that Gap1 functions as a specific chaperone for Gap3. The N-terminal interacting domains of Gap1 mediated the Gap3 stability and Fap1 biogenesis. Gap1 homologues from Streptococcus agalactiae and Staphylococcus aureus also interacted with and stabilized corresponding Gap3 homologues, suggesting that the chaperone activity of the Gap1 homologues is common in biogenesis of SRRPs.

Akt1 is well known for its role in regulating cell proliferation, differentiation, and apoptosis and is implicated in tumors and several neurological disorders. However, the role of Akt1 in neural development has not been well defined. We have isolated zebrafish akt1 and shown that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. Injection of akt1 morpholinos resulted in loss of neuronal precursors with a concomitant increase in post-mitotic neurons, indicating that knockdown of Akt1 is sufficient to cause premature differentiation of neurons. A similar phenotype was observed in embryos deficient for Notch signaling. Both the ligand (deltaA) and the downstream target of Notch (her8a) were downregulated in akt1 morphants, indicating that Akt1 is required for Delta-Notch signaling. Furthermore, akt1 expression was downregulated in Delta-Notch signaling-deficient embryos and could be induced by constitutive activation of Notch signaling. In addition, knockdown of Akt1 was able to nullify the inhibition of neuronal differentiation caused by constitutive activation of Notch signaling. Taken together, these results provide in vivo evidence that Akt1 interacts with Notch signaling reciprocally and provide an explanation of why Akt1 is essential for the inhibition of neuronal differentiation.

Background

While the function of the phosphoprotein (P) gene of the rabies virus (RABV) has been well studied in laboratory adapted RABVs, the genetic diversity and evolution characteristics of the P gene of street RABVs remain unclear. The objective of the present study was to investigate the mutation and evolution of P genes in Chinese street RABVs.

Results

The P gene of 77 RABVs from brain samples of dogs and wild animals collected in eight Chinese provinces through 2003 to 2008 were sequenced. The open reading frame (ORF) of the P genes was 894 nucleotides (nt) in length, with 85-99% (80-89%) amino acid (nucleotide) identity compared with the laboratory RABVs and vaccine strains. Phylogenetic analysis based on the P gene revealed that Chinese RABVs strains could be divided into two distinct clades, and several RABV variants were found to co circulating in the same province. Two conserved (CD1, 2) and two variable (VD1, 2) domains were identified by comparing the deduced primary sequences of the encoded P proteins. Two sequence motifs, one believed to confer binding to the cytoplasmic dynein light chain LC8 and a lysine-rich sequence were conserved throughout the Chinese RABVs. In contrast, the isolates exhibited lower conservation of one phosphate acceptor and one internal translation initiation site identified in the P protein of the rabies challenge virus standard (CVS) strain. Bayesian coalescent analysis showed that the P gene in Chinese RABVs have a substitution rate (3.305x10-4 substitutions per site per year) and evolution history (592 years ago) similar to values for the glycoprotein (G) and nucleoprotein (N) reported previously.

Conclusion

Several substitutions were found in the P gene of Chinese RABVs strains compared to the laboratory adapted and vaccine strains, whether these variations could affect the biological characteristics of Chinese RABVs need to be further investigated. The substitution rate and evolution history of P gene is similar to G and N gene, combine the topology of phylogenetic tree based on the P gene is similar to the G and N gene trees, indicate that the P, G and N genes are equally valid for examining the phylogenetics of RABVs.

To evaluate the role of aflatoxin B1 (AFB1) exposure on risk of hepatocellular carcinoma (HCC), a case-control study nested within a community-based cohort was conducted. Baseline blood and urine samples were used to determine the level of AFB1-albumin adducts and urinary AFB1 metabolites. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the effect of AFB1 exposure on risk of HCC. The adjusted-ORs (95%CIs) were 1.54 (1.01–2.36) and 1.76 (1.18–2.58), respectively, for those with AFB1-albumin adducts and urinary AFB1 metabolites levels above the mean compared to those with levels below the mean. When compared to subjects in the lowest quartile of urinary AFB1 metabolites, there was an increase in risk of HCC, with adjusted ORs (95% CIs) of 0.57 (0.14–2.43), 1.43 (0.32–6.42) and 4.91 (1.18–20.48; Ptrend=0.02), respectively, among noncarriers of hepatitis B virus (HBV) infection. The adjusted OR (95%CI) was 7.49 (5.13–10.93) for carriers of HBsAg compared to noncarriers, regardless of AFB1 status. The ORs (95%CI) were 10.38 (5.73–18.82) and 15.13 (7.83–29.25), for carriers of HBsAg with levels of AFB1-albumin adducts and urinary AFB1 metabolites above the mean, respectively. The combined effect of aflatoxin exposure and HBV infection did not differ by duration of follow-up. Consistent with our previous study with fewer subjects, these data demonstrate that AFB1 exposure is a risk factor for HCC risk. However, in this larger study, the effect of combined AFB1 exposure and HBV infection is more consistent with an additive than a multiplicative model.

Epigenetic modifications may be one mechanism linking early life factors, including parental socioeconomic status (SES), to adult onset disease risk. However, SES influences on DNA methylation patterns remain largely unknown. In a US birth cohort of women, we examined whether indicators of early life and adult SES were associated with white blood cell methylation of repetitive elements (Sat2, Alu and LINE-1) in adulthood. Low family income at birth was associated with higher Sat2 methylation (β = 19.7, 95% CI: 0.4, 39.0 for lowest vs. highest income quartile) and single parent family was associated with higher Alu methylation (β = 23.5, 95% CI: 2.6, 44.4), after adjusting for other early life factors. Lower adult education was associated with lower Sat2 methylation (β = -16.7, 95% CI: -29.0, -4.5). There were no associations between early life SES and LINE-1 methylation. Overall, our preliminary results suggest possible influences of SES across the life-course on genomic DNA methylation in adult women. However, these preliminary associations need to be replicated in larger prospective studies.

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined. Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein. Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P > 0.05) between subjects with normal OGTT (n = 39), impaired glucose tolerance and/or fasting glucose (n = 17), or T2D (n = 36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P < 0.001), fasting insulin (P = 0.02), glycated hemoglobin (P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.001). Follistatin was positively correlated with HOMA-IR alone (P = 0.01). Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

The Hint1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. Previous studies in mice provided evidence that Hint1 may be haplosufficient with respect to its function as a tumor suppressor. In the present study, we investigated the aberrant methylation of Hint1 and explored possible relationships between aberrant methylation and clinicopathological features in hepatocellular carcinoma (HCC). Hypermethylation of Hint1 was evaluated by the methylation specific PCR (MSP) method in 40 patients with HCC (tumor and paired adjacent non-tumor tissues) from Taiwan, 22 cases of normal liver tissue (14 from Taiwan and 8 from the U.S.). HINT1 expression in tissues was detected by immunohistochemistry. The frequencies of hypermethylation of Hint1 in tumor, paired adjacent non-tumor and normal liver tissue were 55.0%, 37.5% and 9.1%, respectively. A statistically significant inverse association was found between Hint1 methylation status and expression of the HINT1 protein in tumor tissues (p<0.003). The relationship between Hint1 methylation status and clinical features and other, previously measured biomarkers was also analyzed. p16 hypermethylation was statistically significantly associated with Hint1 methylation status (p=0.035). There were no correlations between Hint1 methylation and HBV or HCV infection status or AFB1- and PAH-DNA adduct levels. These results suggest that promoter hypermethylation of Hint1 may play a role in hepatocarcinogenesis.

The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR) is composed of two domains (Fap1-NRα and Fap1-NRβ) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NRα and Fap1-NRβ domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NRα at pH 5.0 to 3.0 Ǻ resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates ‘opening’ and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.

Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. Our previous work reveals positive effects of Mozart K.448 in reducing epileptiform discharges in epileptic children. In this study, we evaluated the effect of Mozart K.545 and compared the effects with those of Mozart K.448 on epileptiform discharges in children with epilepsy. Thirty-nine epileptic children with epileptiform discharges were included in the study. They received electroencephalogram examinations before, during, and after listening to Mozart K.448 and K.545, one week apart, respectively. The frequencies of epileptiform discharges were compared. There was a significant decrease in the frequency of epileptiform discharges during and right after listening to Mozart K.448 and K.545 (reduced by 35.7 ± 32.7% during Mozart K.448 and 30.3 ± 44.4% after Mozart K.448; and 34.0 ± 39.5% during Mozart K.545 and 31.8 ± 39.2% after Mozart K.545). Spectrogrammatic analysis of the two pieces of music demonstrated that both share similar spectrogrammatic characteristics. Listening to Mozart K.448 and K.545 decreased the epileptiform discharges in epileptic children. This suggests that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy. Other music with lower harmonics may also decrease epileptiform discharges in epileptic children.

Context

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world but with a striking geographical variation in incidence; most of the burden is in developing countries. This geographic variation in HCC incidence might be due to geographic differences in the prevalence of various etiological factors.

Evidence Acquisition

Here, we review the epidemiological evidence linking dietary exposure to aflatoxin B1 (AFB1) and risk of HCC, possible interactions between AFB1 and hepatitis B virus (HBV) or polymorphisms of genes involved in AFB1-related metabolism as well as DNA repair.

Results

Ecological, case-control and cohort studies that used various measures of aflatoxin exposure including dietary questionnaires, food surveys and biomarkers are summarized.

Conclusions

Taken together, the data suggest that dietary exposure to aflatoxins is an important contributor to the high incidence of HCC in Asia and sub-Saharan Africa, where almost 82% of the cases occur.

Kynurenic acid (KYNA), an astrocyte-derived metabolite, antagonizes the α7 nicotinic acetylcholine receptor (α7nAChR) and, possibly, the glycine co-agonist site of the NMDA receptor at endogenous brain concentrations. As both receptors are involved in cognitive processes, KYNA elevations may aggravate, whereas reductions may improve, cognitive functions. We tested this hypothesis in rats by examining the effects of acute up- or downregulation of endogenous KYNA on extracellular glutamate in the hippocampus and on performance in the Morris water maze (MWM). Applied directly by reverse dialysis, KYNA (30–300 nM) reduced, whereas the specific kynurenine aminotransferase-II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA; 0.3–3 mM) raised, extracellular glutamate levels in the hippocampus. Co-application of KYNA (100 nM) with ESBA (1 mM) prevented the ESBA-induced glutamate increase. Comparable effects on hippocampal glutamate levels were seen after intra-cerebroventricular (i.c.v.) application of the KYNA precursor kynurenine (1 mM, 10 μl) or ESBA (10 mM, 10 μl), respectively. In separate animals, i.c.v. treatment with kynurenine impaired, whereas i.c.v. ESBA improved, performance in the MWM. I.c.v. co-application of KYNA (10 μM) eliminated the pro-cognitive effects of ESBA. Collectively, these studies show that KYNA serves as an endogenous modulator of extracellular glutamate in the hippocampus and regulates hippocampus-related cognitive function. Our results suggest that pharmacological interventions leading to acute reductions in hippocampal KYNA constitute an effective strategy for cognitive improvement. This approach might be especially useful in the treatment of cognitive deficits in neurological and psychiatric diseases that are associated with increased brain KYNA levels.

Background

Nurses are an indispensable component of the work force in the health care system. However, many of them are known to work in a stressful environment which may affect their mental well-being; the situation could be worse in rapidly transforming societies such as China. The purpose of this study was to investigate anxiety symptoms and the associated factors in Chinese nurses working in public city hospitals.

Methods

A cross-sectional survey was performed for Chinese nurses in public city hospitals of Liaoning Province, northeast China. Seven hospitals in different areas of the province were randomly selected for the study. The Zung Self-Rating Anxiety Scale was used to measure anxiety symptoms. Effort-reward imbalance questionnaire and Job Content Questionnaire were used to assess the work stressors. Univariate analysis and stepwise multivariate logistic regression analysis were used to identify the factors associated with anxiety symptoms.

Results

All registered nurses in the seven city hospitals, totaling 1807 registered nurses were surveyed. Of the returned questionnaires, 1437 were valid (79.5%) for analysis. Utilizing the total raw score ≥ 40 as the cut-off point, the prevalence of anxiety symptoms in these nurses was 43.4%. Demographic factors (education, chronic disease and life event), lifestyle factors (regular meals and physical exercise), work conditions (hospital grade, job rank, monthly salary, nurse-patient relationships, job satisfaction and intention of leaving), job content (social support and decision latitude), effort-reward imbalance and overcommitment were all significantly related to the anxiety symptoms. Multivariate logistic regression analysis showed main factors associated with anxiety symptoms were lower job rank (OR 2.501), overcommitment (OR 2.018), chronic diseases (OR 1.541), worse nurse-patient relationship (OR 1.434), higher social support (OR 0.573), lower hospital grade (OR 0.629), taking regular meals (OR 0.719) and higher level of job satisfaction (OR 0.722).

Conclusions

A large proportion of Chinese nurses working in public city hospitals had anxiety symptoms, which warrants immediate investigation and intervention from the hospital administrators. Meanwhile, results of the study suggest that proper counseling, promotion of healthy lifestyle behavior and improvements to the social environment in the work place may be helpful toward reducing or preventing the anxiety symptoms.

Summary

Biotransformation of arsenic includes oxidation, reduction, methylation and conversion to more complex organic arsenicals. Members of the class of arsenite [As(III)] S-adenosylmethyltransferase enzymes catalyze As(III) methylation to a variety of mono-, di- and trimethylated species, some of which are less toxic than As(III) itself. However, no methyltransferase gene has been identified in plants.Here, an arsM gene from the soil bacterium Rhodopseudomonas palustris was expressed in Japonica rice (Oryza sativa L.) cultivar Nipponbare, and the transgenic rice produced methylated arsenic species, which were measured by inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS).Both monomethylarsenate [MAs(V)] and dimethylarsenate [DMAs(V)] were detected in the root and shoot of transgenic rice. After 12-d exposure to As(III), the transgenic rice gave off 10-fold more volatile arsenicals.The present study demonstrates that expression of an arsM gene in rice induces arsenic methylation and volatilization, providing a potential stratagem for phytoremediation theoretically.

Background

A key factor underlying the control of the cellular growth, size and proliferation involves the regulation of the total protein synthesis. Most often, the initial stages of mRNA translation are rate limiting, which involves a group of eukaryotic translation initiation factors (EIFs). Research advances focused on the inhibition of their expression and activity hold the key to the initiation and progression of tumor and tumor prognosis.

Method

We performed RNA interference (RNAi) with the lentivirus vector system to silence the EIF3B gene using the colon cancer cell strain SW1116. The negative control included the normal target cells infected with the negative control virus whereas the knockdown cells included the normal target cells transfected with the RNAi target virus. We tested the inhibition resulting from the decreased expression of EIF3B gene on the proliferation rate of SW1116 cells, including the cell cycle, apoptosis and clonability.

Results

Compared with the negative control, the impact of EIF3B gene expression in SW1116 cells on the levels of mRNA and protein in the knockdown group, was significantly inhibited (P <0.01). Furthermore, the cell proliferation rate and clonability were also significantly inhibited (P <0.01). The apoptosis rate increased significantly (P <0.05). A significant decrease in the number of cells in the G1 phase (P <0.01) and significant increases in S (P <0.01) and G2 phases (P <0.05) were observed.

Conclusions

The silencing of EIF3B gene expression inhibits the proliferation of colon cancer cells.

SUMMARY

Metabolites in the kynurenine pathway of tryptophan degradation are thought to play an important role in neurodegenerative disorders such as Alzheimer’s disease and Huntington’s disease. Metabolites that cause glutamate receptor-mediated excitotoxicity and free radical formation are elevated in the blood and vulnerable brain regions in these diseases, while levels of the neuroprotective metabolite kynurenic acid are often decreased. Here we describe the synthesis and characterization of JM6, a novel small-molecule pro-drug inhibitor of kynurenine 3-monooxygenase (KMO). JM6 raises kynurenic acid and reduces extracellular glutamate in the brain after chronic oral administration by inhibiting KMO in blood. In a transgenic mouse model of Alzheimer’s disease, JM6 prevented spatial memory deficits, anxiety-related behavior, and synaptic loss. JM6 also extended life span, prevented synaptic loss, and decreased microglial activation in a mouse model of Huntington’s disease. These findings support a critical link between blood cells and neurodegeneration that is mediated by KMO and the kynurenine pathway.

Fap1, a serine-rich repeat glycoprotein (SRRP), is required for bacterial biofilm formation of Streptococcus parasanguinis. Fap1-like SRRPs are found in many Gram-positive bacteria and have been implicated in bacterial fitness and virulence. A conserved five-gene cluster, secY2-gap1-gap2-gap3-secA2, located immediately downstream of fap1, is required for Fap1 biogenesis. secA2, gap1, and gap3 encode three putative accessory Sec proteins. SecA2 mediates export of mature Fap1, and Gap1 and Gap3 are required for Fap1 biogenesis. Interestingly, gap1 and gap3 mutants exhibited the same phenotype as a secA2 mutant, implying that Gap1 and Gap3 may interact with SecA2 to mediate Fap1 biogenesis. Glutathione S-transferase pulldown experiments revealed a direct interaction between SecA2, Gap1, and Gap3 in vitro. Coimmunoprecipitation analysis demonstrated the formation of a SecA2-Gap1-Gap3 complex. Homologues of SecA2, Gap1, and Gap3 are conserved in many streptococci and staphylococci. The corresponding homologues from Streptococcus agalactiae also interacted with each other and formed a protein complex. Furthermore, the Gap1 homologues from S. agalactiae and Streptococcus sanguinis rescued the Fap1 defect in the Gap1 mutant, indicating the functional conservation of the accessory Sec complex. Importantly, canonical SecA interacted with the accessory Sec protein complex, suggesting that the biogenesis of SRRPs mediated by the accessory Sec system is linked to the canonical Sec system.

In the cation of the title salt, C24H24N7 3+·3C6H2N3O7 −·2C2H3N, the three benzimidazolium ring systems are oriented to each other at dihedral angles of 10.42 (7), 23.98 (7) and 22.17 (7)°. In the crystal, the cation links to the adjacent picrate anions via N—H⋯O hydrogen bonds; one of independent acetonitrile solvent mol­ecules is also linked to the cation via an N—H⋯N hydrogen bond.